Hakobyan, SvetlanaTortajada Alonso, AgustínHarris, Claire L.de Cordoba, Santiago R.Morgan, Bryan P.2025-01-152025-01-152010-10-01Hakobyan S, Tortajada A, Harris CL, de Córdoba SR, Morgan BP. Variant-specific quantification of factor H in plasma identifies null alleles associated with atypical hemolytic uremic syndrome. Kidney Int. 2010 Oct;78(8):782-8. doi: 10.1038/ki.2010.275. Epub 2010 Aug 11. PMID: 20703214; PMCID: PMC3252682.10.1038/ki.2010.275https://hdl.handle.net/20.500.14352/114423Atypical hemolytic uremic syndrome (aHUS) is associated with complement alternative pathway defects in over half the cases. Point mutations that affect complement surface regulation are common in factor H (CFH); however, sometimes individuals have null mutations in heterozygosis. The latter are difficult to identify, although a consistently low plasma factor H (fH) concentration is suggestive; definitive proof requires demonstration that the mutant sequence is not expressed in vitro. Here, novel reagents and assays that distinguish and individually quantify the common factor H-Y402H polymorphic variants were used to identify alleles of the CFH gene, resulting in low or null expression of full-length fH and also normal or increased expression of the alternative splice product factor H-like-1 (FHL-1). Our assay identified three Y402H heterozygotes with low or absent fH-H402 but normal or increased FHL-1-H402 levels in a cohort of affected patients. Novel mutations explained the null phenotype in two cases, which was confirmed by family studies in one. In the third case, family studies showed that a known mutation was present on the Y allele. The cause of reduced expression of the H allele was not found, although the data suggested altered splicing. In each family, inheritance of low expression or null alleles for fH strongly associated with aHUS. Thus, our assays provide a rapid means to identify fH expression defects without resorting to gene sequencing or expression analysis.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.1038/ki.2010.275https://www.kidney-international.org/article/S0085-2538(15)54638-3/fulltexthttps://pubmed.ncbi.nlm.nih.gov/20703214/open access575Factor H del complemento /Predisposición genética a la enfermedadGenotipoSíndrome hemolítico urémicoBiología molecular (Biología)2412 Inmunología